The present invention relates to the field of immunology.
An allergy can refer to several kinds of unwanted immune reactions including Type I and Type III hypersensitivities. In both types granulocytes, a subset of leukocytes, are involved in the pathogenesis of these diseases. Leukocytes consist of different cell types that all origin from stem cells in the bone marrow. They are further subdivided into lymphocytes (T-cells, B-cells, natural killer cells), myeloid cells (monocytes, macrophages) and granulocytes (eosinophils, neutrophils, and basophils). Mast cells are closely related to basophils and are often regarded as the tissue residing type of a granulocyte. Therefore, in the following granulocytes are defined as eosinophils, neutrophils, basophils, and mast cells. Granulocytes are part of the innate immune response, an unspecific reaction towards pathogens, such as bacteria. This is also reflected by the fact that lipopolysacharide (LPS, component of bacterial cell wall) activation of granulocytes results in a pronounced release of cytokines, such as tumour necrosis factor alpha (TNF-alpha). Activation of granulocytes with either IgE- (type I allergy) or IgG complexes (type III allergy), results in a strong and fast reaction against otherwise innocuous agents (pollen, food, reactions against own structures and tissues such in autoimmune diseases). Mast cells and basophils are the cellular basis for type I allergies (IgE-mediated allergies via the Fc□RI), neutrophils are involved in type III allergies (immune complex mediated reactions, via the Fc□RIII) including autoimmune diseases such as psoriasis, arthritis, immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AHA) and systemic lupus erythematosus (SLE), and contributes to other autoimmune diseases such as rheumatoid arthritis (RA), type I diabetes and multiple sclerosis. Allergies of both types can result in symptoms as benign as a runny nose, to severe chronic diseases and also to life-threatening anaphylactic shock or septic shock.
Type I allergies are commonly treated by corticosteroids (cortisone), anti-histamines, ephinephrine, theophylline or mast cell stabilizers. These compounds block the action of allergic mediators, preventing activation of cells and degranulation processes. These drugs help alleviate the symptoms of allergy but play little role in chronic alleviation of the disorder. All of these therapeutical classes have quite substantial side-effects especially after long-term use. Allergies have an increasing incidence in the western hemisphere with about 20% of the population being affected now. A review and recommendation for treatment of allergic rhinitis has been published by the British National Prescribing Center: MeReC Bulletin Volume 9, Number 3, 1998. Another treatment form of allergies involves the intravenous injection of monoclonal anti-IgE antibodies. Hyposensitization is a form of immunotherapy where the patient is gradually vaccinated against progressively larger doses of the allergen in question. This can either reduce the severity or eliminate hypersensitivity altogether. It relies on the progressive skewing of IgG production, as opposed to the excessive IgE production seen in hypersensitivity type I cases. Allergic diseases type III are commonly treated by steroids, non-steroid anti-inflammatory drugs, methotrexate, and TNF-alpha blocker (receptor analogs or antibodies).
Some autoimmune diseases such as psoriasis or blistering diseases are further complicated by secondary infections of the skin. In contrast to acute injuries of the skin, where antibiotics are usually applied, secondary infections that are the result of chronic disorder such as psoriasis are often left untreated. As a consequence the inflammatory process is worsened and the disease progresses. In both types of hypersensitivities, however, there is still a strong medical need as many of these substances are not suited for a chronic application or the treatment is too expensive for broad use (biological substances). Psoriasis or rheumatoid arthritis belong to the most common autoimmune diseases with 1-2% of the population being affected.
Sirtori (Pharmacological Research 44 (3) (2001): 183-193) discloses an anit-inflammatory effect of aescin which is effected by the reduction of vascular permeability which can reduce the density of leucocytes in affected tissue.
Matsuda et al. (Bioorganic & Medicinal Chemistry Letters 7 (13) (1997): 1611-1616) mention an antiinflammatory effect of isolated escin compounds from horse chestnut which is based on vascular constriction measured through an anti-swelling effect in carragenin induced oedemas in rats.
Dattner (Dermatologic Therapy 16 (2003): 106-113) discusses horse chestnuts in the field of herbal medicine with an anti-inflammatory and vasoprotective effect. An elastase-inhibitory activity is attributed to escin.